The experimental work of Huang et al. [Huang, W., Bahman, A., Torres, J.H., LeBaron R.G., Athanasiou, K.A., 2003. Temporal effects of cell adhesion on mechanical characteristics of the single chondrocyte. J. Orthop. Res. 21, 88-95] provides a novel experimental characterisation of the force required to detach single chondrocytes from a flat substrate with a horizontally moving probe. Measurements reveal that the force required to detach cells spread for six hours is eleven times greater than that required to detach cells spread for one hour. However, it is not clear if this phenomenon is entirely due to geometric changes of chondrocytes during spreading and the consequent increase in adhesion area between cell and substrate. The current computational study, using experimentally measured cell geometries and a cohesive zone model to simulate the cell-substrate interface, reveals that this is not the case. It is demonstrated that both an increase in cell stiffness and an increase in the cell-substrate interface strength during cell spreading are necessary to explain the experimental measurements. It is also revealed that the mechanism of cell detachment involves exclusively tangential debonding, with no lifting of the cell taking place at the cell-substrate interface. Finally, the effect of discrete focal adhesion regions on cell detachment is considered. (c) 2007 Elsevier Ltd. All rights reserved.